A pleural effusion is a collection of fluid within the pleural cavity, a
thin space that exists between the chest wall and the lungs. Various disease
states can lead to accumulation of fluid within this cavity.

STUDY OBJECTIVE: To clarify the clinical significance of pleural effusion
in the clinical course of acute aortic dissection (AAD).

DESIGN: Retrospective clinical series.

SETTING: A university hospital.

PATIENTS: Fifty-five patients strongly suspected of having AAD because
of severe chest or back pain. Patients with obvious ischemic heart disease,
lung disease, and pleural disease were excluded.

INTERVENTIONS: An additional diagnosis of pleural effusion was made
when evident by CT.

MEASUREMENTS AND RESULTS: Pleural effusion was detected in 42 of 48
patients (88%) with AAD (mean plus minus SD age, 65 plus minus 12 years;
35 men and 13 women), but in only 1 of 7 patients (14%) who proved not
to have AAD (mean age, 74 +/- 10 years; 6 men and 1 woman). Effusion
appeared at a mean of 4.5 days after onset of dissection. Thoracentesis
performed in six patients showed a bloody effusion in three patients
and an exudative effusion in three patients. In the six AAD patients
without pleural effusion, four patients underwent surgery within 3 days
after onset of dissection. In patients with AAD, effusion was demonstrated
on the first CT after hospital admission in 18 patients, and was bilateral
in 32 patients. WBC count in blood, serum C-reactive protein concentration,
and body temperature were higher in patients with effusion (13,400 +/-
3,600/microL, 18.4 +/- 11.5 mg/dL, and 38.2 +/- 0.7 degrees C) than
in those without effusion (10,300 +/- 2,900/microL, 4.5 +/- 4.2 mg/dL,
and 37.0 +/- 1.0 degrees C, respectively).

CONCLUSIONS: Pleural effusion occurs frequently in patients with AAD,
often in association with inflammatory reactions.

Lymphangioleiomyomatosis is a rare and complicated disorder that affects
the young, almost exclusively women. It may be associated with the tuberous
sclerosis complex, which includes renal angiolipoma, chylothorax and
lymph node myomatosis. Its clinical pulmonary manifestations vary from
simple cough to the development of recurrent pneumothoraces, hemoptysis,
and even complicated pleural effusions.

Progressive dyspnea develops as the disease evolves. Eventually most
patients require lung transplantation. This wide array of symptoms and
signs makes the differential diagnosis extensive, and the clinician
must be familiar with this disorder to arrive promptly to the correct
diagnosis.

We report a case of a 36-year-old woman with a long history of recurrent
pleuritic chest pain with associated dyspnea before being diagnosed
with lymphangioleiomyomatosis. A review of the literature pertinent
to this case is provided.

LUNG CANCER

The significance of intraoperative pleural effusion during surgery for
bronchogenic carcinoma.

METHODS: From 1993 to 1999, 1279 patients received thoracotomy with
curative intent for primary lung carcinoma. Intraoperatively, 52 patients
(4%) presented a PE >100ml which was not diagnosed preoperatively.
Of these, seven patients had received preoperative transthoracic fine-needle
biopsy FNB and were excluded from the analysis. In the remaining 45
patients pleural fluid cytology was undertaken. In patients with cytology-negative
PE, clinico-pathologic characteristics including intratumoral vascular
invasion, intratumoral perineural invasion, peritumoral lymphocytic
infiltrate, visceral, parietal and mediastinal pleural involvement,
pTNM and survival were analyzed and compared with our total population
of lung cancer patients operated on during the same period.

RESULTS: The mean amount of collected fluid was 210ml (100-450ml).
Of the 45 patients with intraoperative PE, 16 (35%) received exploratory
thoracotomy because of pleural carcinosis or major involvement of mediastinal
structures; eight (18%) received resection of the tumor, although the
cytologic examination of the pleural fluid eventually resulted positive
for neoplastic cells. Median survival for the two groups was 6 and 9
months, respectively. Twenty-one patients (47%) received resection of
the tumor with a cytology-negative pleural fluid. In this group, analysis
of clinico-pathologic characteristics revealed that squamous cell type
and mediastinal pleural involvement were significantly associated with
the presence of intraoperative PE (P=0.01 and P=0.05, respectively);
3- and 5-year survivals of this group were similar to those observed
in our total population of resected lung cancer patients (68 and 56%
vs. 54 and 42%, P=0.27).

CONCLUSIONS: The presence of a PE at thoracotomy during surgery for
lung carcinoma is an infrequent occurrence. In more than 50% of the
cases cytology is positive and prognosis is poor. In the remaining cases,
however, cytology is negative and the PE should be considered as reactive;
in these patients a curative resection can be accomplished with an anticipated
chance of long-term survival.

Asthma and Allergy Research Institute, University of Western Australia,
Perth, Australia; Wellcome Trust Centre for Human Genetics, University
of Oxford, Oxford, United Kingdom.

Curr Opin Pulm Med 2002 Jul;8(4):294-301 Abstract quote

Pleural effusion is common in clinical practice. Increased vascular
permeability and leakage play a principal role in the development of
exudative pleural effusions. In vitro and in vivo evidence have solidly
established vascular endothelial growth factor (VEGF), a potent inducer
of vascular permeability, as a crucial mediator in pleural fluid formation.
VEGF is present in high quantities in human effusions.

In the pleural space, mesothelial cells, infiltrating inflammatory
cells, and (in malignant pleuritis) cancer cells contribute to the VEGF
accumulation in the pleural fluids. Pleural fluid VEGF is biologically
active and may promote tumor growth and chemotaxis. Strategies to antagonize
the VEGF activity at various target points of its signaling pathway
have shown success in vitro and in animal models of malignant pleural
or peritoneal effusions. Novel agents targeting VEGF activities are
undergoing clinical trials.

Regulation of VEGF activity and vascular permeability represent a rapidly
expanding field of research, which is likely to provide further insight
in the pathophysiology of pleural fluid formation.

LABORATORY/RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

GENERAL

New criteria for the differentiation between transudates and exudates.

AIMS: To investigate whether cholesterol and lactate dehydrogenase
(LDH) measurements in fluids are more sensitive and specific markers
for differentiating between exudates and transudates, as confirmed clinically,
than the measurement of fluid total protein concentrations alone.

PATIENTS/METHODS: Serum, pleural fluid, and ascitic fluid from 61 unselected
patients were analysed retrospectively for LDH, cholesterol, and total
protein. Clinical classification of transudate or exudate was reached
independently by reviewing clinical details and laboratory data.

RESULTS: Of 54 samples (40 pleural fluid and 14 ascitic fluid), 30
were classified clinically as exudates and 24 as transudates. Fluid
LDH and fluid to serum protein ratio measurements were equally good
at differentiating between exudates and transudates, with a sensitivity
of 90%, a specificity of 79%, a positive predictive value (PPV) of 84%,
and a negative predictive value (NPV) of 86%. A combination of these
parameters improved sensitivity to 100% and NPV to 100%, but lowered
the specificity to 71% and PPV to 81%. This combination achieved a higher
efficiency than Light's criteria.

CONCLUSION: Routine measurement of fluid LDH values and the calculation
of fluid to serum total protein ratios will aid in differentiating exudates
from transudates.

Department of Thoracic Medicine, Medical School, University of Crete,
University General Hospital of Heraklion, Crete, Greece

Chest 2002 Mar;121(3):815-20 Abstract quote

STUDY OBJECTIVES: Interleukin (IL)-1alpha, IL-6, and tumor necrosis
factor (TNF)-alpha were measured in pleural fluid from 57 patients with
pleural effusion in order to evaluate the diagnostic utility of these
cytokines. We studied 20 patients with malignant pleural effusion, 11
patients with parapneumonic pleural effusion, 9 patients with tuberculous
pleural effusion, and 17 patients with transudative pleural effusion.
Cytokines were measured by radioimmunoassay.

SETTING: University tertiary hospital.

RESULTS: The mean values of the three cytokines measured in pleural
fluid or in serum were significantly higher in patients with exudates
than with transudates (p < 0.05). The ratio of IL-6 in pleural fluid
to serum was significantly higher in exudates than in transudates (p
< 0.05). The level of IL-6 in pleural fluid was significantly higher
in tuberculous than malignant (p < 0.007) or parapneumonic pleural
effusions (p < 0.04). No significant difference between the three
types of exudates was found in pleural fluid levels of IL-1alpha or
TNF-alpha.

CONCLUSIONS: Serum levels of IL-1alpha, TNF-alpha, and in particular
IL-6 can distinguish exudates from transudates, while pleural fluid
IL-6 levels could be useful as an additional marker in the differential
diagnosis of tuberculous, malignant, and parapneumonic exudates. Finally,
our results suggest that there is local cytokine production in exudative
pleural effusions.

Medical University of South Carolina (Drs. Heffner and Sahn), Charleston,
SC.

Chest 2002 Jun;121(6):1916-20 Abstract quote

Study objectives: To determine multilevel likelihood ratios for pleural
fluid tests that are commonly used to discriminate between exudative
and transudative pleural effusions.

DESIGN: Meta-analysis of patient-level data. Patient data: Selected
studies included patients with diagnoses of exudative or transudative
pleural effusions who underwent thoracentesis and laboratory analysis
of their pleural fluid. Measurements and methods: Studies were identified
by searching MEDLINE and related bibliographies. Data were obtained
for 1,448 patients from seven primary investigators or extracted from
dot plots in published reports. Likelihood ratios were calculated from
extracted data stratified across ranges of test result values. R

ESULTS: Sufficient data were available to calculate multilevel likelihood
ratios for the elements of Light's criteria (pleural fluid lactate dehydrogenase
[LDH], ratio of pleural fluid to serum LDH, and ratio of pleural fluid
to serum protein), pleural fluid protein, ratio of pleural fluid to
serum cholesterol, pleural fluid cholesterol, and gradient of pleural
fluid to serum albumin. Each of these tests provided levels of likelihood
ratios through the most clinically relevant range (0 to 10).

CONCLUSION: Multilevel likelihood ratios combined with a clinician's
estimation of the pretest probability of an exudative effusion improve
the diagnostic accuracy of discriminating between exudative and transudative
pleural effusions. Likelihood ratios avoid the use of confusing terms,
such as "pseudoexudates," that derive from the use of single
cutoff points for pleural fluid tests.

AMYLASE

Amylase levels in pleural effusions: a consecutive unselected series
of 841 patients.

STUDY OBJECTIVES: To describe the causes and relative frequency of
amylase-rich pleural effusion (ARPE), and to study the origin and histologic
type of the tumors with ARPE, the strength of the association between
ARPE and the result of pleural cytology, and whether pleural amylase
(PA) is a prognostic factor in the survival of patients with a malignant
pleural effusion.

RESULTS: There were 66 ARPEs: 40 neoplastic, and 26 benign with tuberculosis,
pancreatitis, and liver cirrhosis as the most frequent causes. Thirty-six
percent of patients in our series and 61% of patients with ARPE had
a neoplastic disease (odds ratio [OR], 3; p < 0.001); this association
got much stronger for cases with PA levels > or = 600 IU/L (95th
percentile); [OR, 10; p < 0.001]. The most frequent tumor origin
was lung cancer (13 cases). Adenocarcinoma was the most frequent histologic
type (18 cases). Two mesothelioma effusions were ARPEs. There was a
positive association between ARPE and the finding of tumor cells in
pleural fluid (OR, 2.79; p < 0.01). In the malignant group, PA levels
> or = 600 IU/L identified a group of patients with quite a short
median survival (p = 0.016).

CONCLUSIONS: The most common cause of ARPE was neoplasm. There was
a positive association between ARPE and malignancy, stronger with the
highest levels (95th percentile). Lung cancer and adenocarcinoma were
the most common tumor and histologic type associated with ARPE. Mesothelioma
may also produce ARPE. There was an association between ARPE and the
finding of tumor cells in the pleural fluid. The highest PA levels identified
a group of patients with a median shorter survival.

Comparative genomic hybridization (CGH) is a molecular cytogenetic
technique that provides an overview on chromosomal imbalances within
the whole tumor cell genome. This method has yet not been applied in
effusion cytology.

We performed CGH analysis in malignant effusions, fine needle aspirates,
and imprint smears from eight ovarian adenocarcinomas, three breast
carcinomas, one colon adenocarcinoma, and three malignant mesotheliomas.
In part, CGH analysis from fresh frozen tissue and classic karyotyping
served as controls. In this series, 14/15 cytologic specimens were suitable
for extraction of high molecular weight DNA sufficient for reliable
CGH analysis. CGH profiles from cytologic material were equal or even
more significant in comparison with corresponding fresh frozen tumor
samples. We conclude that CGH analysis from cytologic specimens may
support the primary cytologic diagnosis of malignancy, especially in
the differential diagnosis of benign proliferating mesothelium, malignant
mesothelioma, and metastatic adenocarcinoma. CGH analysis of metastatic
lesions may provide information on the site of the primary tumors and
detects cytogenetic imbalances affecting oncogenes and tumor suppressor
genes involved in tumor progression and metastatic spread.

BACKGROUND: Tests able to help in the diagnostic work-up of pleural
exudates are needed. C-reactive protein (CRP) may be useful for distinguishing
between benign and malignant exudates.

METHODS: A total of 123 consecutive patients diagnosed as having exudative
pleural effusion (60 associated with malignancy and 63 benign effusions)
were included in the study. Sensitivity, specificity, positive and negative
predictive values (PV+, PV-), and positive and negative likelihood ratios
(LR+, LR-) were established at different cut-off points.

CONCLUSIONS: The pleural CRP level provides useful information for
the study of pleural exudates. A level below 20 mg/l suggests a malignant
origin and a level above 45 mg/l virtually rules out this possibility.
Additional advantages of measuring CRP level are that it is an inexpensive
test and is easy to perform.

FLOW CYTOMETRY

Detection of Malignant Epithelial Cells in Effusions
Using Flow Cytometric Immunophenotyping
An Analysis of 92 Cases

Ben Davidson, MD, PhD, etal

Am J Clin Pathol 2002;118:85-92 Abstract quote

We compared the efficiency of immunophenotyping using flow cytometry
(FCM) and a combination of morphologic and immunocytochemical studies
for detecting malignant cells in 92 effusions.

Cytologic results were as follows: carcinoma cells, 43 specimens; benign,
42 specimens; suggestive of nonepithelial malignancy, 7 specimens. After
immunocytochemical analysis, 5 benign specimens were reclassified as
malignant and 4 malignant epithelial specimens as benign. With FCM,
cells positive for Ber-EP4, B72.3, AH6, and HB-TN were detected in 28
to 36 (64%-82%) of 44 carcinomas but only 2 to 12 (5%-29%) of 41 benign
specimens. Significant association was seen for coexpression. Ber-EP4
and AH6 were the most sensitive; Ber-EP4 was the most specific. The
presence of cells positive for 3 of 4 markers strongly suggested malignancy
(34/44 carcinoma specimens [77%]; 3/41 reactive specimens [7%]). The
presence of cells positive for all 4 markers was diagnostic of malignancy
(17/44 malignant specimens [39%]; 0/41 reactive effusions [0%]). FCM
and immunocytochemical results for Ber-EP4 expression showed excellent
association.

FCM is a powerful tool for diagnosing difficult effusions and can
quantify coexpression of various markers in fresh specimens. By using
established cellular markers coupled with biological markers, FCM also
has great promise for experimental purposes.

GROSS APPEARANCE/
CLINICAL VARIANTS

CHARACTERIZATION

GENERAL

VARIANTS

CHYLOTHORAX

PYOTHORAX ASSOCIATED LYMPHOMA

Pyothorax-associated lymphoma: a review of 106 cases.

Nakatsuka S, Yao M, Hoshida Y, Yamamoto S, Iuchi K, Aozasa
K.

Department of Pathology, Osaka University Graduate School of
Medicine, Suita, Japan.

J Clin Oncol 2002 Oct 15;20(20):4255-60 Abstract quote

PURPOSE: Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma
developing in the pleural cavity after a long-standing history of pyothorax.
Full details of PAL are provided here.

PATIENTS AND METHODS: Clinical and pathologic findings were reviewed
in 106 patients with PAL collected through a nationwide survey in Japan.

RESULTS: Age of the patients with PAL was 46 to 82 years (median, 64
years), with a male/female ratio of 12.3:1. All patients had a 20- to
64-year (median, 37-year) history of pyothorax resulting from artificial
pneumothorax for treatment of pulmonary tuberculosis (80%) or tuberculous
pleuritis (17%). The most common symptoms on admission were chest and/or
back pain (57%) and fever (43%). Laboratory data showed that the serum
neuron-specific enolase level was occasionally elevated (3.55 to 168.7
ng/mL; median, 18.65 ng/mL), suggesting a possible diagnosis of small-cell
lung cancer. Histologically, PAL usually showed a diffuse proliferation
of large cells of B-cell type (88%). In situ hybridization study showed
that PAL in 70% of the patients was Epstein-Barr virus (EBV)-positive.
PAL was responsive to chemotherapy, but the overall prognosis was poor,
with a 5-year survival of 21.6%.

CONCLUSION: This study established the distinct nature of PAL as a
disease entity. PAL is a non-Hodgkin's lymphoma of exclusively B-cell
phenotype in the pleural cavity of patients with long-standing history
of pyothorax, and is strongly associated with EBV infection. Development
of PAL is closely related to antecedent chronic inflammatory condition;
therefore, PAL should be defined as malignant lymphoma developing in
chronic inflammation.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER

CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

WT1, Estrogen Receptor, and Progesterone Receptor as
Markers for Breast or Ovarian Primary Sites in Metastatic Adenocarcinoma
to Body Fluids

We evaluated these markers for cytology cell-block preparations from
96 effusion specimens (metastases from 29 breast, 22 ovarian, and 45
adenocarcinomas from other sites). WT1 protein was reactive in 19 cases
metastatic from ovary (86%), 2 from breast (7%), and none from other
sites (specificity, 97%). Of the metastatic breast carcinomas, 21 (72%)
were reactive for ER, 15 (52%) for PR, and 13 (45%) for both (combined
specificity, 84%). GCDFP was reactive in only 4 breast cancer cases
(14%). Ovarian tumors also were frequently positive for ER (19 [86%]),
PR (11 [50%]), or both (10 [45%]). WT1 protein is an effective marker
for ovarian adenocarcinoma, especially in ascites.

The detection of ER and PR in metastatic adenocarcinoma from pleural
or pericardial effusions can distinguish breast from lung primary sites.
Reactivity for ER and PR did not distinguish between breast and ovarian
metastases; however, studies for WT1 protein and GCDFP may aid in making
this distinction.

BACKGROUND: Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing
transcription factor selectively expressed in thyroid, lung and diencephalon.
It has been shown to label pulmonary adenocarcinoma, thyroid tumors,
and small cell carcinoma (pulmonary and extrapulmonary) with relatively
high sensitivity and specificity. The usefulness of this immunostain
in cytology specimens has not been thoroughly discussed in the literature.

METHODS: The authors evaluated 36 effusion cytology cases (17 pleural
effusion, 18 ascitic fluid, and 1 pericardial effusion) diagnosed as
metastatic adenocarcinoma and with cell blocks prepared from the file
of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a three-year
period from 1998 to early 2001. The clinical, radiologic, cytologic,
and histologic (if any) findings were reviewed. A provisional diagnosis
of the primary site was deduced for each of the 36 cases by clinical,
radiologic, and/or histologic correlation. Immunohistochemical study
was performed on the cell block sections of the effusion cytology specimens
using mouse monoclonal antibody against TTF-1, after microwave heat-antigen
retrieval. The results were correlated with the primary origin of the
metastatic adenocarcinoma.

CONCLUSIONS: The current study validates TTF-1 as a highly sensitive
and specific immunomarker for distinguishing between metastatic pulmonary
and extrapulmonary adenocarcinoma in effusion cytology specimens, which
are known to be associated with intrinsic artifact due to less than
ideal cellular preservation.

DIFFERENTIAL DIAGNOSIS

KEY DIFFERENTIATING FEATURES

CHYLOUS EFFUSION

The lipoprotein profile of chylous and nonchylous pleural effusions.

Staats BA, Ellefson RD, Budahn LL, Dines DE, Prakash UB, Offord
K.

Mayo Clin Proc 1980 Nov;55(11):700-4 Abstract quote

The lipoprotein electrophoregrams and the cholesterol and triglyceride
levels of the pleural fluid were evaluated for patients with chylous
pleural effusions, as defined by the presence of a distinctive band
of chylomicrons on the lipoprotein electrophoregram, and in patients
with nonchylous effusions of various causes.

One hundred forty-one patients were studied during a 3-year period.
The chylous effusions had strikingly higher triglyceride levels (median
249, range 49 to 2,270 mg/dl) than the nonchylous group (median 33,
range 13 to 107 mg/dl); there were no significant differences in cholesterol
or protein between the two groups. The gross description of the fluid
was a poor indicator of its origin, being described as consistent with
chyle in less than 50% of cases of chylous effusions. The triglyceride
values distinguished chylous effusion from nonchylous effusion; values
greater than 110 mg/dl are highly suggestive of a chylous effusion.
Equivocal cases--triglyceride values between 50 and 110 mg/dl--required
lipoprotein analysis.

Pleural effusions of undetermined cause, regardless of gross appearance
of the fluid, require that a screening triglyceride value be obtained
to rule out a chylous effusion.

OBJECTIVE: A panel was convened by the Health and Science Policy Committee
of the American College of Chest Physicians to develop a clinical practice
guideline on the medical and surgical treatment of parapneumonic effusions
(PPE) using evidence-based methods.

OPTIONS AND OUTCOMES CONSIDERED: Based on consensus of clinical opinion,
the expert panel developed an annotated table for evaluating the risk
for poor outcome in patients with PPE. Estimates of the risk for poor
outcome were based on the clinical judgment that, without adequate drainage
of the pleural space, the patient with PPE would be likely to have any
or all of the following: prolonged hospitalization, prolonged evidence
of systemic toxicity, increased morbidity from any drainage procedure,
increased risk for residual ventilatory impairment, increased risk for
local spread of the inflammatory reaction, and increased mortality.
Three variables, pleural space anatomy, pleural fluid bacteriology,
and pleural fluid chemistry, were used in this annotated table to categorize
patients into four separate risk levels for poor outcome: categories
1 (very low risk), 2 (low risk), 3 (moderate risk), and 4 (high risk).
The panel's consensus opinion supported drainage for patients with moderate
(category 3) or high (category 4) risk for a poor outcome, but not for
patients with very low (category 1) or low (category 2) risk for a poor
outcome. The medical literature was reviewed to evaluate the effectiveness
of medical and surgical management approaches for patients with PPE
at moderate or high risk for poor outcome. The panel grouped PPE management
approaches into six categories: no drainage performed, therapeutic thoracentesis,
tube thoracostomy, fibrinolytics, video-assisted thoracoscopic surgery
(VATS), and surgery (including thoracotoiny with or without decortication
and rib resection). The fibrinolytic approach required tube thoracostomy
for administration of drug, and VATS included post-procedure tube thoracostomy.
Surgery may have included concomitant lung resection and always included
postoperative tube thoracostomy. All management approaches included
appropriate treatment of the underlying pneumonia, including systemic
antibiotics. Criteria for including articles in the panel review were
adequate data provided for >/=20 adult patients with PPE to allow
evaluation of at least one relevant outcome (death or need for a second
intervention to manage the PPE); reasonable assurance provided that
drainage was clinically appropriate (patients receiving drainage were
either category 3 or category 4) and drainage procedure was adequately
described; and original data were presented. The strength of panel recommendations
on management of PPE was based on the following approach: level A, randomized,
controlled trials with consistent results or individual randomized,
controlled trial with narrow confidence interval (CI); level B, controlled
cohort and case control series; level C, historically controlled series
and case series; and level D, expert opinion without explicit critical
appraisal or based on physiology, bench research, or "first principles."

EVIDENCE: The literature review revealed 24 articles eligible for full
review by the panel, 19 of which dealt with the primary management approach
to PPE and 5 with a rescue approach after a previous approach had failed.
Of the 19 involving the primary management approach to PPE, there were
3 randomized, controlled trials, 2 historically controlled series, and
14 case series. The number of patients included in the randomized controlled
trials was small; methodologic weaknesses were found in the 19 articles
describing the results of primary management approaches to PPE. The
proportion and 95% CI of patients suffering each of the two relevant
outcomes (death and need for a second intervention to manage the PPE)
were calculated for the pooled data for each management approach from
the 19 articles on the primary management approach.

Malignant pleural effusions contribute to considerable morbidity in
cancer patients and generally portend an overall poor prognosis. Treatment
of malignant pleural effusions is palliative; therefore, quality of
life issues, as well as the risks and benefits of the therapeutic options,
become more critical.

In my opinion, factors such as in patient versus outpatient management
and associated procedural discomfort are important in the decision-making
process, and the patient should participate in these subjective considerations.
It is difficult to compare results and determine the true efficacy of
different techniques and agents because endpoints and response criteria
as well as the extent and method of follow-up vary. In addition, the
etiology of the primary complaint, dyspnea, is frequently multifactorial.
However, malignant effusions recur, and therefore repeated thoracentesis,
especially if the fluid rapidly reaccumulates, is usually not a good
long-term solution unless the patient's overall prognosis and current
condition prohibits a more invasive option. The standard option for
recurrent effusions is insertion of a chest tube. If the lung re-expands,
chemical pleurodesis is attempted to achieve adherence of the visceral
to the parietal pleura.

Sterilized talc is the best sclerosant; it has good efficacy and cost
effectiveness and can be administered easily as a slurry at the bedside
via a chest tube with minimal patient discomfort and without more aggressive
and invasive procedures.

Section of Vascular and Interventional Radiology, Department of
Radiology, Yale University School of Medicine, New Haven, Connecticut,
USA.

Curr Opin Pulm Med 2002 Jul;8(4):302-7 Abstract quote

Malignant pleural effusion is a significant cause of morbidity and
a poor prognostic indicator. Traditional treatments have variable success
and significant drawbacks, including a length of stay in the hospital.

Alternatively, a tunneled pleural catheter permits long-term drainage
as an outpatient, cost-effectively controlling the effusion and related
symptoms in over 80 to 90% of patients. Other advantages are the ability
to treat trapped lungs and large locules. Spontaneous pleurodesis may
occur in over 40% of patients, and the catheter can be used to administer
sclerosant or antineoplastic agents. Complications tend to be minor
and easily managed.

A tunneled pleural catheter should be considered for all patients with
MPE having a reasonable expectancy of being an outpatient.

STUDY OBJECTIVE: To examine the effectiveness of repeated intrapleural
chemotherapy using an implantable access system (INFUSE-A-PORT; Horizon
Medical Products; Manchester, GA) for the management of a malignant
pleural effusion (MPE).

METHODS: Twenty-two patients with histologically proven MPEs (11 men
and 11 women; mean age, 63.8 years; age range, 51 to 81 years; performance
status, less-than-or-equal 3) were enrolled in this study. There were
17 patients with MPEs resulting from primary lung cancer; of whom 7
had metastatic disease (stage IV), 3 had stage IIIB disease, and 7 had
postoperative recurrences. Three patients had MPEs that were caused
by mesothelioma, and two had MPEs caused by breast cancer. Intrapleural
catheters were placed by a video-assisted thoracoscopic procedure. The
intrapleural administration of 5-fluorouracil (5-FU; 250 mg per body)
and cisplatin (10 mg per body) using the implantable access system was
performed biweekly at the outpatient clinic. Drainage of the MPEs through
the port was performed only when the patients had some manifestations
that occurred due to increasing effusion.

RESULTS: The mean total administered doses of 5-FU and cisplatin were
3,290 and 124 mg, respectively. The mean follow-up period was 431 days
(range, 209 to 792 days). The median survival period was 403 days, and
the longest survival period was 792 days. No treatment-related mortality,
renal dysfunction, bone marrow suppression, or infection occurred. One
patient experienced a hemothorax after eight instances of intrapleural
administration. The port and the catheter were involved with the tumor
in one patient.

CONCLUSIONS: Repeated intrapleural chemotherapy using the implantable
access system is useful and safe for patients with MPEs. In the future,
prospective randomized studies will be necessary to compare the efficacy
of therapy for MPE using the implantable access system with that of
pleurodesis

Departments of Thoracic Medicine, Thoracic Surgery, and Clinical
Pharmacology, Medical School, University of Crete, and University General
Hospital, Heraklion, Crete, Greece.

Am J Respir Crit Care Med 1999 Jan;159(1):37-42 Abstract
quote

Intrapleural administration of fibrinolytic agents has been shown to
be effective and safe in the treatment of loculated parapneumonic pleural
effusions. However, controlled studies of the possible role of the activity
of urokinase (UK) through the volume effect are lacking. We therefore
investigated the hypothesis that UK is effective through the lysis of
pleural adhesions and not through the volume effect.

Thirty-one consecutive patients with multiloculated pleural effusions
were randomly assigned to receive either intrapleural UK (15 patients)
or normal saline (NS) (16 patients) for 3 d, in a double-blind manner.
All patients had inadequate drainage through a chest tube (< 70 ml/24
h). UK was given daily through the chest tube in a dose of 100.000 IU
diluted in 100 ml of NS. Controls were given the same volume of NS intrapleurally.
Response was assessed by clinical outcome, fluid drainage, chest radiography,
pleural ultrasonography (US) and/or computed tomography (CT). Clinical
and radiographic improvement was noted in all but two patients in the
UK group but in only four in the control group. The net mean volume
drained during the 3-d treatment period was significantly greater in
the UK group (970 +/- 75 ml versus 280 +/- 55 ml, p < 0.001). Pleural
fluid drainage was complete in 13 (86.5%) patients in the UK group (two
patients were treated through video-assisted thoracoscopy) but in only
four (25%) in the control group. Twelve patients in the control group
were subsequently treated with UK and six of them had complete drainage;
the remaining six patients had complete drainage after video-assisted
thoracoscopy.

Our results suggest that UK is effective in the treatment of loculated
pleural effusions through the lysis of pleural adhesions and not through
the volume effect.

Induction of pleurodesis offers benefit for patients with metastatic
tumors and symptomatic malignant pleural effusions, but the best method
for achieving this is still unknown.

In this prospective, randomized comparison of two well-established
pleurodesis procedures, 36 patients with malignant pleural effusions,
expanded lungs after drainage, and expected survival of > 1 mo received
either bleomycin instillation (60E) via a small-bore thoracostomy tube
or thoracoscopic talc poudrage (5 g) under local anesthesia. Efficacy,
safety, and cost could be evaluated for 32 treatments (17 bleomycin,
15 talc) in 31 patients. Recurrence rates of effusion with bleomycin
and talc poudrage after 30 d were 41% and 13% (p = 0.12), respectively,
those after 90 d were 59% and 13%, respectively (p = 0.01), and those
after 180 d were 65% and 13% (p = 0.005), respectively. Neither procedure
showed any major adverse effect, and both were equally well tolerated.
Cost estimation favored thoracoscopic talc poudrage, both for the initial
hospitalization and with regard to recurrences.

In conclusion, thoracoscopic talc pleurodesis under local anesthesia
is superior to bleomycin instillation for pleurodesis in cases of malignant
pleural effusion.

Distribution of talc suspension during treatment of malignant pleural
effusion with talc pleurodesis.

Talc pleurodesis is an effective technique for the management of symptomatic
malignant pleural effusions. It is assumed that a good dispersion of
talc suspension contributes to the final success of this treatment.

For this purpose, guidelines often advise to rotate the patient after
intra-pleural instillation of the sclerosant. This prospective, randomized
study analyses the dispersion of talc suspension and the overall success
rate in patients with malignant effusions. After instillation of 99mTc-sestamibi-labeled
talc suspension ten subjects were rotated for 1 h, while the ten other
patients remained in a stable supine body position. Scintigraphic imaging
was done in two directions immediately after instillation and after
1 h with a clamped drain. The overall success of the treatment was assessed
1 month after the pleurodesis. The dispersion of talc was limited and
unequal in 75% of the subjects. In two patients with apparently good
distribution on anterior views, the lateral views of the scintigraphy
showed only limited distribution. Rotation of the patients did not influence
the dispersion of sludge after 1 min or 1 h. Pleurodesis was successful
in 85% of the patients after 1-month follow-up.

Standard rotation protocols for patients with malignant pleural effusion
do not affect the overall dispersion of talc suspension and should be
abolished because of the discomfort caused to the patients.